Sodium Hydroxide → 5-Fluoro-2-methyl-1H-indole-3-carbaldehyde

HRID 2375299Notes

Reaction equation

HRID 2375299 reaction equation
O=P(Cl)(Cl)Cl.[F:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11]([CH3:16])=[CH:10]2.[OH-:17].[Na+].[CH3:19]O.C(Cl)Cl>CN(C=O)C>[F:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11]([CH3:16])=[C:10]2[CH:19]=[O:17]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 27787155-Fluoro-2-methylindoleHCID 21226129Dichloromethane methanol

Product 1

HCID 64841155-Fluoro-2-methyl-1H-indole-3-carbaldehydeYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Dry DMF (0.6 mL) was added slowly to POCl3 (0.9 mL) at room temperature under nitrogen atmosphere, and the mixture stirred for 5 minutes. 5-fluoro-2-methyl-1H-indole (149 mg, 1.0 mmol) was dissolved in 5 mL dry DMF and added slowly to the rapidly stirring mixture to keep the temperature below 35° C. After stirring for 2 h at room temperature, the reaction mixture was poured into 30 mL ice water. The aqueous layer was basified (30 mL 1.0 N NaOH) and extracted into methylene chloride. The organic layer was washed with water (1×50 mL), brine (1×50 mL), and dried over Na2SO4. The solvent was removed in vacuo to yield an off-white solid. The solid was brought up in 1:3 MeOH/methylene chloride and filtered through a short plug of silica to remove colored impurities. The dried-down solid was then washed with dry acetonitrile to provide the product 5-fluoro-2-methyl-1H-indole-3-carbaldehyde as a crystalline white solid (105 mg, 55% yield) after drying. 1H NMR (400 mHz, DMSO-d6) δ 12.10 (s, 1H), 10.03 (s, 1H), 7.72 (dd, J=9.7, 2.6 Hz, 1H), 7.38 (dd, J=8.8, 4.5 Hz, 1H), 7.01 (dt, J=9.2, 2.6 Hz, 1H), 3.34 (s, 1H), 2.68 (s, 3H).

Workup

  1. additionadded slowly to the
  2. stirringrapidly stirring mixture
  3. customthe temperature below 35° C
  4. stirringAfter stirring for 2 h at room temperature
  5. extractionextracted into methylene chloride
  6. washThe organic layer was washed with water (1×50 mL), brine (1×50 mL)
  7. dry with materialdried over Na2SO4
  8. customThe solvent was removed in vacuo
  9. customto yield an off-white solid
  10. filtrationfiltered through a short plug of silica
  11. customto remove colored impurities
  12. washThe dried-down solid was then washed with dry acetonitrile

Sources & evidence

ORD record
ord-66e84db26d5c41bebfdc0f25ed3b8def
Source dataset
uspto-grants-2008_12
Patent number
US07465738B2

Reaction notes

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